Interleukin-1β regulates urokinase plasminogen activator (u-PA), u-PA receptor, soluble u-PA receptor, and plasminogen activator inhibitor-1 messenger ribonucleic acid expression in cultured human endometrial stromal cells

Abstract

The interleukin-1 (IL-1) system plays an integral role in local intercellular interactions during implantation. In addition, the plasminogen activator system, especially urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI-1), and u-PA receptor (u-PAR), are crucial during embryo implantation. Decidualization and implantation are complex processes dependent upon several proteases, including u-PA, and IL-1 is known to affect PA activity in several cell types. We investigated the role of IL-1β in regulating u-PA, PAI-1, u-PAR, and soluble u-PAR messenger ribonucleic acid (mRNA) expression in cultured human endometrial stromal cells using quantitative competitive PCR. For confirmation of the mRNA data, we measured PAI-1 and u-PAR protein by enzyme-linked immunosorbent assay. Confluent stromal cell cultures treated with progesterone and estradiol for 9 days were stimulated with IL-1β, and IL-1β plus IL-1β antibody for an additional 24 h. Total RNA was extracted, reverse transcribed, and coamplified using quantitative and competitive PCR with internal standards. IL-1β increased PAI-1, u-PAR, and soluble u-PAR expression in a dose-dependent manner, and this result was reversed by anti-IL-1β antibody treatment, u-PA mRNA expression was not dependent on IL-1β. These results suggest that IL-1 may be important in regulating PAI-1 and u-PAR during stromal cell decidualization before implantation.